Muscle relaxant drugs are known to affect the transmission of nerve impulses to muscle fibers by either (a) blocking the acetylcholine induced depolarization of the post junctional membrane of the myoneural unit (i.e., a non-depolarizing muscle relaxant) or (b) promoting and prolonging depolarization to prevent the return of the myoneural unit to the resting state and thereby render the muscle refractory to nerve impulse (i.e., a depolarizing muscle relaxant). Structural Forms of Anesthetic Compounds. Hugh S. Mathewson, M.D. (Charles C. Thomas, 1961).
Depolarizing muscle relaxants such as succinylcholine have the major disadvantage that they are not easily reversed by anticholinesterase drugs.
Non-depolarizing agents such as d-tubocurarine and pancuronium are known to have certain drawbacks which limit their effectiveness as muscle relaxants. For example, they maintain paralysis for an undesirably long time and the recovery period is slow. It is not uncommon for anticholinesterase agents such as neostigmine and edrophonium to be employed to antagonize the effects of such muscle relaxants. A further disadvantage of non-depolarizers is that they can cause side-effects such as bradycardia, tachycardia, hypotension, and hypertension and must therefore be carefully administered and controlled.
Applicant has discovered a novel class of compounds described hereinafter which exhibit potent muscle relaxing activity of the non-depolarizing type while exhibiting desirable onset, duration and recovery times. Comparatively less changes in hemodynamic parameters (heart rate, arterial pressure, myocardial contractility and cardiac output) are produced by compounds of the present invention.
It is an object of the present invention to provide novel enamine quaternary compounds which are useful as muscle relaxants.
It is another object of the invention to provide pharmaceutical compositions containing the novel compounds which when administered to warm-blooded animals exhibit muscle relaxing activity.
It is a further object of the invention to provide methods of making the novel enamine quaternary compounds.
It is a further object to provide enamine quaternary intermediates which are valuable building blocks for making novel enamine quaternary muscle relaxants.